Dr. Ganz proposes to test the hypothesis that transgenic expression of antimicrobial peptides targeted to neutrophil granules will enhance the resistance of recipient mice to microbial pathogens. The following aims are proposed: 1) Optimize the expression of defensin and protegrin genes in the mouse cell line 32D c13; 2) Construct transgenic mice that express human defensin; 3) Assay the effects of transgenic peptides on the antimicrobial activity of mouse phagocytes and body fluids against a panel of pathogens; 4) Determine the effect of transgenic antimicrobial peptides on the susceptibility of mice to selected pathogens.